Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Ppublish 14 citations
PubMed: 38940198 DOI: 10.1242/jcs.261566
TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.
J Cell Sci 137(14)
Authors: Ke Zoe Shan, Trieu Le, Pengfei Liang, Ping Dong, Augustus J Lowry, Polina Kremmyda, Lena Claesson-Welsh, Huanghe Yang
Affiliations
- Department of Biochemistry, Duke University, School of Medicine, Durham, NC 27710, USA.
- Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck, Beijer and SciLifeLab Laboratory, Uppsala 751 85, Sweden.
- Department of Neurobiology, Duke University, School of Medicine, Durham, NC 27710, USA.
Abstract
TMEM16F (also known as ANO6), a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes, such as blood coagulation, neurodegeneration, cell-cell fusion and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight the role of intracellular signaling by TMEM16F in endothelial cells but also open new avenues for exploring the regulatory mechanisms for membrane lipid asymmetry and their implications in disease pathogenesis.
MeSH
Cells, Cell Biology, Endothelial Cells, Membranes, Angiogenesis
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